2vja

TORPEDO CALIFORNICA ACETYLCHOLINESTERASE IN COMPLEX WITH A NON HYDROLYSABLE SUBSTRATE ANALOGUE, 4-OXO-N,N,N-TRIMETHYLPENTANAMINIUM (OTMA) - ORTHORHOMBIC SPACE GROUP-DATASET A AT 100K
(see also AChE inhibitors and substrates (Part III))



OTMA is a nonhydrolyzable substrate analogue of AChE. Its hydrolyzis is impossible as OTMA possesses carbon instead ester oxygen of AChE natural substrate ACh. Similarly to ACh, OTMA covalently binds to the TcAChE Ser200 Oγ at the catalytic anionic subsite (CAS). At this subsite OTMA also interacts with Trp84, Phe330 (cation-π interactions); Glu199 (electrostatic interaction); Gly118, Gly119, and Ala201 (hydrogen bonds). Of note, OTMA binds not only at CAS, but also at peripheral anionic subsite (PAS). The second OTMA molecule interacts with Trp279, Tyr70 (cation-π interactions), and Tyr121 (weak hydrogen bond) at this subsite. Thus, this dual binding mode of OTMA with TcAChE (to CAS and PAS) could be prototypical for AChE bivalent inhibitors.

About this Structure
2VJA is a 2 chains structure of sequences from Torpedo californica. Full crystallographic information is available from OCA.

Reference
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